The genetic basis of malignant melanoma is poorly understood. To enhance our understanding of the pathogenesis of this important cancer, we have recently generated a mouse model for cutaneous melanoma wherein activated H-Ras(va1l2) was constitutively expressed in ink4a-null melanocytes. In this proposal, we plan to establish and characterize an inducible Ras melanoma model that will enable us to explore the role of activated H-Ras(vall2) in tumor maintenance, progression and angiogenesis in fully developed melanomas. Furthermore, in order to not only identify the downstream targets/mediators of RAS activation in tumor cells, but to examine the host gene expression response brought about by RAS-dependent, tumor cell-derived stimuli, we will exploit several methodologies proven useful for the analysis and isolation of differentially expressed genes. These methodologies include Affymetrix hybridization arrays, subtractive hybridization and modified differential display. Within the scope of this proposal, array analysis will be the principal approach. The longterm goals will be to gain a comprehensive view of differential patterns of gene expression, to ultimately clone these genes, and to evaluate their biological roles in normal and transformed melanocytes.